Overview:Treponema pallidum
is a spirochetal bacterium often found growing
in clusters (Figure 1). This pathogen has a
central protoplasmic cylinder bound by a
cytoplasmic membrane, a thin layer of
peptidoglycan, and an outer membrane devoid of
transmembrane proteins (Salazar et al.,
2002) (Figure 2). There are three other structurally,
serologically, and morphologically identical
species belonging to the Treponema
genus, namely, T. endemicum, T.
pertenue,and T. carateum.
These species can only be distinguished by
genetic analysis. T. pallidum spiral
shape, rapid rotation about its axis, and two to
three flagella at each end allow a corkscrew
like motility (Figure
3). The bacterium is approximately 6 to 20 μm
(micrometres) in length and only 0.10 to 0.18 μm
in width. It is microaerophilic and
glucose-dependent; without glucose, oxygen
impairs motility. T. pallidum contains
one of the smallest prokaryotic genomes
consisting of about 1000 kilobase pairs, and is responsible
for the sexually transmitted disease,
syphilis.

Figure 1. An
unstained micrograph depicting the growth of
Treponema pallidum in small clusters.

Figure 2. A schematic illustration of
one end of a Treponema pallidum bacterium.

Figure 3. An
anatomical illustration of a Treponema
pallidum bacterium from a lateral
perspective. From a lateral view, one is able to
identify the cellular components along the
length of a T. pallidum bacterium,
which give this spiral bacterium (spirochete) a
unique cellular morphology, and mode of
motility.

Identification:
T. pallidum cannot be
identified using
Gram staining because it is too thin and it cannot
be cultured in vivo, making it difficult to
study in the lab. It may instead be
characterized by several different methods,
including the immunohistochemical
Warthin-Starry-stain (WS-stain),
electron microscopy, dark-field microscopy
(Figure 4), immunofluorescence, or immunoperoxidase techniques with polyclonal
antibodies. A positive darkfield result is an
almost certain diagnosis of primary, secondary,
or early congenital syphilis from suspected
lesions or regional lymph nodes. In primary
syphilis, the darkfield examination may provide
a means by which to identify the etiologic agent
of syphilis and diagnose the disease before
antibodies to T. pallidum can be
detected. The WS-stain shows a positive result
for T. pallidum presence when it stains
a dark brown colour, however this
silver-staining technique presents problems with
false-positives and false-negatives (Martín-Ezquerra
et al., 2009).

Figure 4.
Using a darkfield microscopy technique, this
photomicrograph reveals the presence of
Treponema pallidum spirochetes. Darkfield
microscopy involves the application of light
rays in an oblique manner to microscopic
specimens in order to illuminate these
organisms, which are normally difficult to see
using normal lighting techniques.

Clinical Infections:T. pallidum is an obligate
internal human parasite that is not native to the normal
microflora and has no known non-human
reservoir. Each subspecies causes a different
infection; for instance, T. pallidum causes venereal syphilis,
T. pertenue causes yaws, T. endemicum
causes endemic syphilis (bejel), and T. carateum
causes pinta (Antal et al., 2002). T. pallidum causes infections that may be
divided into early stages (including
primary and secondary lesions) and late stages.
Early stage lesions are
considered infectious and may last up to five years
after the time of infection.
There may be periods of latency between
symptomatic episodes and before the
late stage infection. Pinta only involves
cutaneous lesions, while yaws and
endemic syphilis also affect the mucous
membranes and bones. Venereal
syphilis is capable of affecting most organs and
can cross the placenta (Antal et
al., 2002).

T. pallidum is distributed differently,
depending on the stage of infection and
the infecting species. In primary syphilis
infections, T. pallidum is found in
large numbers in the dermis and surrounding the
vascular walls in a
vasculotropic patterns. In secondary syphilis
infection, this germ is
distributed mainly in the lower layers of the
epidermis in an epitheliotropic
pattern (Martín-Ezquerra et al., 2009)
(Figure 5). Venereal
syphilis is characterized by
genital ulcerations, skin rashes and in later
stages, invasion of the central
nervous system. The other three species of this
genus
commonly cause primary lesions
and disseminated skin or mucous membrane lesions
(Antal et al., 2002).

Transmission:
Transmission of infection varies between the
diseases. Yaws is transmitted by
direct skin contact from a lesion and its
clinical expression varies according to
climatic conditions. Endemic syphilis is
transmitted via direct skin contact
with a lesion or by mucous membrane contact.
Pinta does not have a known
transmission; however, it is suspected to be
direct contact with a lesion.
Venereal syphilis is transmitted via intimate
contact.

T. pallidum has been found to be a synergistic
contributor to the risk of human
immunodeficiency virus (HIV)
infection. Since both HIV and syphilis are
sexually transmitted infections, coinfection
is common between them. Ulcers caused by
syphilis provide an ideal
entry point for the HIV virus and T. pallidum
genetically alters macrophages to
make the individual more susceptible to HIV
(Karp et al., 2009).

T. pallidum reproduces rapidly and can penetrate interjunctionally between
vascular endothelia to gain access to various
tissues. It is also poorly antigenic
due to the fact that possible pathogenic
antigens are hydrophilic and tethered
to the inner cytoplasmic membrane, making them
inaccessible to antibodies
(Salazar et al., 2002). Some of the transmembrane
proteins have been shown to
be porins to destroy host-cells. Antigenic
variation has also been suggested as a mechanism
for persistence and prolonged host infection.

Treatment:
Infections caused by this species can be treated
with various antibiotics, with
penicillin being the most widely used. Ideally, these
infections could be eradicated because they are
not found in any other animal
reservoirs, however poverty and illiteracy on
hygiene make this difficult. Parenteral
penicillin G is the only therapy with documented
effect during pregnancy. For early syphilis, one
dose of penicillin is sufficient. Those who are
allergic to penicillin can effectively be
treated with oral tetracycline or doxycycline;
however, data to support this is limited.
Ceftriaxone may be considered as an alternative
therapy, although the optimal dose is not yet
defined. However, cross-reactions in
penicillin-allergic patients with cephalosporins
such as ceftriaxone are possible. Azithromycin
was suggested as an alternative. However, there
have been reports of treatment failure due to
resistance in some areas.